英夫利西单抗治疗难治性溃疡性结肠炎的临床研究

背景:传统的氨基水杨酸制剂、激素和免疫抑制剂不能满足部分难治性溃疡性结肠炎(UC)患者的治疗需求,生物制剂的出现给这部分患者带来了希望。目的:评估英夫利西单抗对难治性UC的临床疗效。方法:采用回顾性研究方法,收集2012年12月至2014年1月在哈尔滨医科大学附属第二医院住院治疗,因激素无效或激素依赖而使用英夫利西单抗治疗的中、重度活动期UC患者12例。疗程中以改良Mayo评分系统评估UC活动性,以评价英夫利西单抗的临床疗效。结果:12例患者均完成英夫利西单抗治疗并随访38周,临床表现均有不同程度的改善,6周、22周和38周有效率分别为66.7%、83.3%和91.7%,组间差异均有统计学意义(P0.05)。结论:英夫利西单抗对难治性UC疗效较好,具有临床应用价值。     

英夫利西单抗联合硫唑嘌呤治疗中重度克罗恩病的疗效研究

背景:激素和免疫抑制剂是克罗恩病(CD)的传统治疗药物,然而部分CD患者对传统药物耐药或依赖。目的:评价英夫利西单抗联合硫唑嘌呤治疗中重度CD的有效性和安全性。方法:24例CD患者随机分为英夫利西单抗组、硫唑嘌呤组、英夫利西单抗联合硫唑嘌呤组(联合治疗组)。英夫利西单抗组于第0、2、6周给予英夫利西单抗5mg/kg,随后每隔8周给予英夫利西单抗5 mg/kg;硫唑嘌呤组给予硫唑嘌呤2.5 mg/kg qd;联合治疗组给予硫唑嘌呤2.5 mg/kg qd,并于第0、2、6周给予英夫利西单抗5 mg/kg,随后每隔8周给予英夫利西单抗5 mg/kg。治疗第26周末以CD疾病活动指数(CDAI)和内镜检查评价治疗疗效。治疗期间记录患者不良反应发生情况。结果:治疗第26周末,联合治疗组的临床总有效率和内镜下总有效率较英夫利西单抗组和硫唑嘌呤组均显著升高(P<0.05);治疗第26周末联合治疗组血红蛋白水平较治疗前显著升高(P<0.05),ESR和CRP水平治疗前均显著降低(P<0.05);治疗期间联合治疗组无严重不良反应发生。结论:对于激素抵抗或依赖的中重度CD患者,英夫利西单抗联合硫唑嘌呤的疗效优于单用英夫利西单抗或硫唑嘌呤。     

英夫利昔单抗-类克在激素抵抗及激素依赖溃疡性结肠炎治疗中的应用

目的:评价英夫利昔单抗(类克)对于激素抵抗及激素依赖的中重度溃疡性结肠炎(ulcerativecolitis,UC)的治疗效果.方法:回顾性分析2009-04/2011-11在北京大学第一医院及中国人民解放军北京军区总医院消化内科住院治疗的,因激素抵抗或激素依赖而接受类克治疗的中重度UC患者共19例的临床资料.结果:19例患者中10例达到临床缓解,其中2例达到黏膜愈合,7例治疗有效,治疗总有效率是89.47%,缓解率是52.63%;治疗有效者,血红蛋白(hemoglobin,Hb)及白蛋白(albumin,ALB)均明显上升,血沉(erythrocyte sedimentation rate,ESR)及C反应蛋白(Creaction protein,CRP)明显下降.5例具有肠外表现者的肠外症状都得到改善.观察期间未发生严重不良反应.结论:类克对于激素抵抗及激素依赖的中重度UC国人具有良好的治疗效果,同时安全性较好,为难治性UC患者的治疗开拓了新途径.     

肿瘤坏死因子-α拮抗剂治疗中国汉族人群强直性脊柱炎369例不良反应初步研究

目的 旨在评价接受了肿瘤坏死因子(TNF)-α拮抗剂治疗的中国汉族人群强直性脊柱炎(AS)患者的不良反应,为生物制剂的临床治疗提供参考依据.方法 本研究纳入在我科接受了TNF-α拮抗剂治疗的369例中国汉族人群AS患者,未完全跟踪随访给药1011次.所有患者均评估了用药后2h出现的不良反应,对其中126例长期用药患者进行了第8、12、52、104周的随访.观察患者用药后2h的短期不良反应和长期不良反应.采用Fisher确切概率法进行统计分析.结果 接受TNF-α拮抗剂治疗的369例AS患者,随访用药后2h共计发生30次不良反应.英夫利西单抗和重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)引起的短期不良反应发生率差异无统计学意义(分别为3.8％,2.6％,P=0.31).126例患者分别依次进行了第8、12、52、104周的随访,共计39例发生不良反应,长期应用英夫利西单抗和rhTNFR:Fc不良反应发生率差异无统计学意义(分别为49％,51％,P=0.69).结论 中国汉族人群AS患者在接受TNF-α拮抗剂治疗时应注意上述不良反应的发生,尤其应注意第3、4次接受英夫利西单抗治疗患者的不良反应.接受英夫利西单抗和rhTN FR:Fc治疗的患者用药后2h内和长期(≥2年)治疗的不良反应发生相当.     

参苓白术散联合英夫利西单抗治疗老年炎症性肠病的疗效及对炎症因子、肠黏膜屏障和免疫功能的影响

目的探讨参苓白术散联合英夫利西单抗治疗老年炎症性肠病的疗效及对炎症因子、肠黏膜屏障和免疫功能的影响。方法纳入74例老年炎症性肠病患者,按照随机数字表法分为观察组37例与对照组37例。对照组采用英夫利西单抗治疗,观察组在对照组基础上结合参苓白术散治疗。两组疗程均为14 w。比较两组疗效、治疗前后黏膜镜像评分和疾病活动指数(DOI)评分、炎症因子、肠黏膜屏障功能和免疫功能的变化。结果观察组总有效率(94.59%)显著高于对照组(70.27%,P0.05)。治疗后,黏膜镜像评分和DOI评分观察组显著低于对照组(t=10.870、10.623,均P0.05)。治疗后,血清白细胞介素(IL)-6、C反应蛋白(CRP)和肿瘤坏死因子(TNF)-α水平观察组显著低于对照组(t=7.304、11.454、6.642,均P0.05)。治疗后,血清D-乳酸和内毒素水平观察组显著低于对照组(t=12.711、10.208,均P0.05)。治疗后,CD3~+、CD4~+和CD4~+/CD8~+观察组显著高于对照组(t=8.832、12.553、7.672,均P0.05)。结论参苓白术散联合英夫利西单抗治疗老年炎症性肠病患者疗效良好,可减轻患者炎症反应,改善患者肠黏膜屏障功能和免疫功能。     

235例炎症性肠病患者首次接受糖皮质激素治疗的临床疗效分析

目的探讨炎症性肠病(IBD)患者首次接受糖皮质激素(激素)治疗的疗效及疾病转归。方法收集2002年1月-2010年12月我院收治的首次使用激素治疗的IBD患者890例,对激素治疗30 d及随访1年的临床疗效进行回顾性分析。结果 890例IBD患者中,溃疡性结肠炎(UC)患者401例,克罗恩病(CD)患者489例,其中共有81例(81/401,20.2%)UC及154例(154/489,31.5%)CD患者使用口服或静脉滴注激素,激素治疗30 d时,UC患者完全缓解57例(57/81,70.4%),部分缓解22例(22/81,27.2%),无效2例(2/81,2.5%);CD患者完全缓解94例(94/154,61.0%),部分缓解45例(45/154,29.2%),无效15例(15/154,9.7%)。随访1年末,UC患者持续应答53例(53/79,67.1%),激素依赖26例(26/79,32.9%);CD患者持续应答102例(102/151,67.5%),激素依赖26例(26/15,17.2%),手术23例(23/15,15.2%)。激素短期及远期疗效的风险因素回归分析显示合用硫唑嘌呤/6-巯基嘌呤(AZA/6-MP)与CD患者激素治疗的远期疗效相关(P=0.03)。结论大部分IBD患者对激素治疗有效,UC患者激素治疗总有效率优于CD,随访1年32.9%UC及17.2%CD患者呈激素依赖,15.2%CD患者需手术切除病变肠段。     

努力提高溃疡性结肠炎生物治疗的水平

近十年,生物制剂用于顽固性或者重度溃疡结肠炎的治疗取得了较好效果,具有起效快、临床缓解率及黏膜愈合率高及不良反应少等优点,目前应用最广泛、循证证据最丰富的是英夫利西单抗,其次是阿达木单抗,但国内溃疡性结肠炎(ulcerative colitis,UC)生物制剂临床应用很少.本文结合国外文献及我们的经验对UC生物治疗的现状、适应证、禁忌证、使用剂量和疗程、不良反应处理、生物制剂转换治疗等作一介绍,以期提高国内UC生物治疗水平.     

新型生物制剂英夫利西治疗克罗恩病10例

目的 观察新型生物制剂英夫利西(infliximab)治疗10例克罗恩病(CD)患者的疗效及安全性.方法 前瞻性开放性研究英夫利西静脉滴注治疗经常规治疗无效或激素依赖的中、重度活动性CD患者8例和以反复下消化道大出血为主要临床表现的CD患者2例.在第0、2、6周给予5 mg/kg荆量作为诱导缓解,随后每隔8周给予相同剂量维持,临床与内镜随访30周.结果 ①治疗2周时,8例活动性CD患者中5例有效;30周时4例临床缓解(其中3例停用激素),1例有效;②2例以反复下消化道出血为主要临床表现者随访30周无再出血;③30周时复查肠镜6例,其中溃疡完全愈合或基本愈合4例;④7例发生不良事件,其中严重不良反应2例,分别为肺炎和迟发型过敏反应各1例.结论 英夫利西可诱导并维持部分活动性CD缓解,促进CD肠黏膜病变愈合,严重不良反应发生率不高.     

英夫利昔在难治性及合并肠外表现的溃疡性结肠炎中的疗效及安全性分析

目的评价英夫利昔(Infliximab,IFX)对难治性及合并肠外表现的溃疡性结肠炎(ulcerative colitis,UC)的疗效。方法回顾性分析难治性及合并肠外表现的UC住院患者36例,均接受IFX治疗,评价其临床疗效。结果 36例患者中,33例为难治性UC(合并肠外表现5例),3例合并特殊肠外表现(2例合并肛周脓肿,1例合并强直性脊柱炎)。IFX治疗后,13例临床缓解(3例黏膜愈合),16例有效,7例无效。IFX治疗总有效率为80.6%,缓解率为36.1%;8例合并肠外表现者中,5例肠外症状得到改善,有效率为62.5%。观察期间未发生IFX相关的严重不良反应。结论 IFX对难治性UC及合并肠外表现UC患者均有较好的疗效,且安全性较高。     

英夫利西单抗联合甲氨蝶呤治疗老年类风湿关节炎的临床效果

目的观察英夫利西单抗(IFN)联合甲氨蝶呤(MTX)治疗老年类风湿关节炎(RA)的临床效果,探讨提高老年RA临床疗效的药物治疗方案。方法选择80例老年RA患者,按照患者知情同意的原则,分为对照组(n=35)和观察组(n=45),对照组采用MTX治疗,观察组采用英夫利西单抗联合MTX治疗,治疗24 w后比较两组患者临床症状及相关检查指标、临床疗效和不良反应情况。结果治疗24 w后两组患者临床症状及相关检查指标比较,差异显著(P<0.01,P<0.05);两组患者治疗后出现的不良反应例数比较,差异不显著(P>0.05)。结论在老年RA患者药物治疗过程中,可考虑首选IFN联合MTX治疗的方式,可显著提高临床疗效,且不会增加治疗中的不良反应。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.